Ambergris is a high grade perfume which has been used from around the seventh century, and has been also used as a Chinese medicinal drug. Ambergris is considered to be formed by sperm whales due to lithification of indigestibles of foods (octopuses, squids, or the like) by gastrointestinal secretions and excreted therefrom. The detailed production mechanism thereof, however, is unknown. The principal component of ambergris is ambrein, and it is considered that ambrein is subjected to oxidative decomposition by sunlight and oxygen while the ambergris is floating on the ocean's surface, thereby producing compounds having a variety of fragrances.
Although ambrein, the principal component of ambergris, is used as perfumes or pharmaceuticals, it is impossible to obtain a large amount of ambrein as a natural product. A variety of organic synthesis methods have thus been proposed.
For example, as a method of producing (+)-ambrein easily, efficiently, and inexpensively, Japanese Patent Application Laid-Open (JP-A) No. H10-236996 discloses a method comprising a step of producing a new sulfonic acid derivative from ambrenolide and coupling therewith an optically active γ-cyclogeranyl halide.
Tetrahedron Asymmetry, (2006) Vol. 17, pp. 3037-3045 discloses a method of obtaining ambrein by a convergent synthesis using a Julia coupling reaction between 2-((1R,2R,4αS,8αS)-2-(methoxymethoxy)-2,5,5,8α-tetramethyl decahydronaphthalene-1-yl)acetaldehyde synthesized from (±)(5,5,8α-trimethyloctahydro-1H-spiro[naphthalene-2,2′-oxirane]-1-yl)methanol and 5-((4-((S)-2,2-dimethyl-6-methylenecyclohexyl)butane-2-yl)sulfonyl)-1-phenyl-1H-tetrazole synthesized from (±)methyl 6-hydroxy-2,2-dimethyl cyclohexanecarboxylate.
A method in which 3-deoxyachilleol A which is a monocyclic triterpene is obtained from squalene by using a mutant enzyme (D377C, D377N, Y420H, Y420W, or the like) of a squalene-hopene cyclase is also known (Biosci. Biotechnol. Biochem., (1999) Vol. 63, pp. 2189-2198, Biosci. Biotechnol. Biochem., (2001) Vol. 65, pp. 2233-2242, and Biosci. Biotechnol. Biochem., (2002) Vol. 66, pp. 1660-1670).
It is also reported that tetraprenyl-β-curcumene cyclase is a bifunctional enzyme which is involved in two reactions: a reaction in which a tetracyclic C35 terpenol is produced from tetraprenyl-β-curcumene; and a reaction in which a bicyclic triterpene is produced from squalene (J. Am. Chem. Soc., (2011) Vol. 133, pp. 17540-17543).